Translational Control in the Latency of Apicomplexan Parasites

Michael J. Holmes, Leonardo da Silva Augusto, Min Zhang, Ronald Wek, William Sullivan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. use latent stages to persist in the host, facilitate transmission, and thwart treatment of infected patients. Therefore, it is important to understand the processes driving parasite differentiation to and from quiescent stages. Here, we discuss how a family of protein kinases that phosphorylate the eukaryotic initiation factor-2 (eIF2) function in translational control and drive differentiation. This translational control culminates in reprogramming of the transcriptome to facilitate parasite transition towards latency. We also discuss how eIF2 phosphorylation contributes to the maintenance of latency and provides a crucial role in the timing of reactivation of latent parasites towards proliferative stages. Latent stages are critical to both pathogenesis and transmission of apicomplexan parasites.Differentiation into a latent stage can be induced by stress, which is sensed by eIF2 kinases that initiate the integrated stress response.The integrated stress response causes a decrease in general protein synthesis that diverts energy into the preferential translation of certain mRNAs likely to drive progression to latency.Translational control helps to maintain parasite latency until transmission, after which the process is reversed and proliferation resumes.

Original languageEnglish (US)
JournalTrends in Parasitology
DOIs
StateAccepted/In press - 2017

Fingerprint

Parasites
Eukaryotic Initiation Factor-2
Plasmodium
Toxoplasma
Protein Biosynthesis
Transcriptome
Protein Kinases
Phosphotransferases
Maintenance
Phosphorylation
Proteins
Therapeutics

Keywords

  • EIF2
  • Latency
  • Plasmodium
  • Toxoplasma
  • Translational control

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Translational Control in the Latency of Apicomplexan Parasites. / Holmes, Michael J.; Augusto, Leonardo da Silva; Zhang, Min; Wek, Ronald; Sullivan, William.

In: Trends in Parasitology, 2017.

Research output: Contribution to journalArticle

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